A Study of BMS-986466 With Adagrasib With or Without Cetuximab in Participants With Kirsten Rat Sarcoma Virus Glycine 12 to Cysteine (KRAS G12C)-Mutant Solid Tumors

Phase 1/2 Open-label Study of BMS-986466 in Combination With Adagrasib With or Without Cetuximab in Participants With KRAS G12C-mutant Advanced Solid Tumors

The purpose of this study is to find a safe, tolerable, and efficacious dose of BMS-986466 when given orally, in combination with adagrasib with or without cetuximab in participants with advanced KRAS G12C-mutant non-small cell lung cancer (NSCLC), pancreatic duct adenocarcinoma (PDAC), biliary tract cancer (BTC), or colorectal cancer (CRC).

Study Overview

• Status: Terminated
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: Cetuximab; Drug: BMS-986466; Drug: Adagrasib

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Local Institution - 0053
• Finland
  • Helsinki, Finland, 00029
    • Local Institution - 0083
• France
  • Lille, France, 59037
    • Local Institution - 0020
• Israel
  • HaMerkaz
    • Petah Tikva, HaMerkaz, Israel, 4941492
      • Local Institution - 0082
  • Tell Abīb
    • Tel Aviv, Tell Abīb, Israel, 6423906
      • Local Institution - 0081
• United States
  • California
    • Los Angeles, California, United States, 90067
      • Local Institution - 0047
  • Georgia
    • Athens, Georgia, United States, 30607
      • Local Institution - 0040
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Local Institution - 0025
    • Morristown, New Jersey, United States, 07960
      • Local Institution - 0008

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Key Inclusion Criteria:

Part 1:

• Individuals with a confirmed diagnosis of advanced KRAS G12C mutant NSCLC, CRC, PDAC and BTC that has spread to other parts of the body and cannot be removed surgically, may or may not have received previous treatment with KRAS G12C inhibitors.
• For NSCLC and CRC: Individuals must have a documented KRAS G12C mutation status from NYS or FDA approved/cleared or CE marked test or, when such result is not available, positive KRAS G12C mutation status should be confirmed by a central laboratory in blood sample collected at the time of screening.
• For PDAC and BTC: Participants must have a documented KRAS G12Cmutation from NYS or FDA-approved/cleared, or CE-marked test and blood samples will be collected only for retrospective testing.
• Are relapsed or refractory to available standard of care treatments.

Part 2:

• Individuals with a confirmed diagnosis of advanced KRAS G12C-mutant NSCLC (Part 2A) or CRC (Part 2B) that has spread to other parts of the body and cannot be removed surgically and have not received previous treatment with KRAS inhibitors.
• Individuals must have a documented KRAS G12C mutation from FDA or NYS approved/ cleared or CE marked test or, when such result is not available, positive KRAS G12C mutation status should be confirmed by a central laboratory in blood sample and /or tumor samples collected at the time of screening or from archival biopsies (less than 1 year old).
• Have failed or disease recurrence or are not able to tolerate after at least 1 pervious line of therapy.

Key Exclusion Criteria:

• Have tumors with known BARF V600X, PTPN11 or KRASQ61X mutations.
• Have or any significant heart disease or condition.
• Receiving any medications that are substrate of CYP3A4 or inducers and/ or inhibitors

Note: Other protocol-defined inclusion/exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: DDI Cohort	Drug: BMS-986466; Specified dose on specified days; Other Names: IACS-15509; BBP-398; Drug: Adagrasib; Specified dose on specified days; Other Names: MRTX849; KRAZATI®
Experimental: Part 1: Dose Escalation	Drug: Cetuximab; Specified dose on specified days; Other Names: Erbitux®; Drug: BMS-986466; Specified dose on specified days; Other Names: IACS-15509; BBP-398; Drug: Adagrasib; Specified dose on specified days; Other Names: MRTX849; KRAZATI®
Experimental: Part 2: Dose Expansion	Drug: Cetuximab; Specified dose on specified days; Other Names: Erbitux®; Drug: BMS-986466; Specified dose on specified days; Other Names: IACS-15509; BBP-398; Drug: Adagrasib; Specified dose on specified days; Other Names: MRTX849; KRAZATI®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of Participants With Dose Limiting Toxicity (DLTs)	A DLT was defined as: Death not related to disease progression; Grade (Gr) 4 (Life-threatening) neurotoxicity; Gr 3 (Severe) neurotoxicity of greater than 7 days; Gr 3 neurotoxicity does not revert to baseline within 28 days of the start date of the Grade 3 event; Seizures of grade that do not resolve within 7 days; Gr 4 cytokine release syndrome (CRS) that does not resolve to less than or equal to Gr 3 within 3 days; Gr 3 CRS that does not resolve to less than or equal to Grade 2 within 7 days; Any increase in aspartate aminotransferase (AST) or ALT \> 3 Ã- ULN and concurrent increase in total bilirubin \> 2 Ã- ULN that is unrelated to CRS and has no other probable reason to explain the combination of increases; Any other Gr 3 or 4 event deemed unexpected by the Investigator and considered a DLT upon evaluation by the safety review committee	Cycle 1 (Each cycle consist of 28 days)
Part 1: Number of Participants With Adverse Events (AEs)	An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.	From first dose until 100 days after last dose (Up to approximately 5 months)
Part 1: Number of Participants With Serious Adverse Events (SAEs)	A SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability or permanent damage, is a congenital anomaly/birth defect, is an important medical event.	From first dose until 30 days after last dose (Up to approximately 3 months)
Part 1: Number of Participants With AEs Leading to Discontinuation	An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatmen	From first dose until 30 days after last dose (Up to approximately 3 months)
Part 1: Number of Participants Who Died	Death due to any cause was assessed.	From first dose until 100 days after last dose (Up to approximately 5 months)
Part 2 Objective Response Rate (ORR) Assessed by Blinded Independent Central Review (BICR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	Objective Response Rate (ORR) is defined as the percentage of participants with a confirmed Best overall response of Complete Response (CR) or Partial Response (PR) by RECIST v1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	From randomization untill disease progression or death, whichever occurs first (up to approximately 5 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Maximum Observed Plasma Concentration (Cmax)	Blood samples were collected to assess adequate PK profiles. Participants were not enrolled in Part 1a, 1b.	Cycle 1 Day 1 (Each cycle consist of 28 days)
Part 1: Time to Maximum Concentration (Tmax)	Blood samples were collected to assess adequate PK profiles. Participants were not enrolled in Part 1a, 1b.	Cycle 1 Day 1 (Each cycle consist of 28 days)
Part 1: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-T])	Blood samples were collected to assess adequate PK profiles. Participants were not enrolled in Part 1a, 1b.	Cycle 1 Day 1 (Each cycle consist of 28 days)
Part 2-Progression-free Survival (PFS) Assessed by BICR as Per RECIST v1.1	Progression-Free Survival then (PFS) is defined as the time between the date of randomization and the date of first documented disease progression, based on Investigator assessments (per RECIST v1.1), or death due to any cause, whichever occurs first Calculated using Kaplan-Meier estimates. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	From randomization untill disease progression or death, whichever occurs first (up to approximately 5 months)
Part 2- Disease Control Rate (DCR) Assessed by BICR as Per RECIST v1.1	Disease Control Rate (DCR) (as per Recists v1.1) is defined as the number of randomized participants who achieve a BOR of confirmed CR, confirmed PR, or stable disease (SD), based on BICR assessments divided by the number of all randomized participants.	From randomization untill disease progression or death, whichever occurs first (up to approximately 5 months)
Part 2- Duration of Response (DOR) Assessed by BICR as Per RECIST v1.1	Duration of objective response (DoR) is defined as the time between the date of first confirmed response (CR or PR) to the date of the first documented tumor progression (per RECIST 1.1) per BICR assessment, or death due to any cause, whichever occurs first. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	From randomization untill disease progression or death, whichever occurs first (up to approximately 5 months)
Part 2- Time to Response (TTR)	Time to response (TTR) is defined as the time, in months, from randomization to the first objective documentation of PR or better assessed per BICR. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.	From randomization untill disease progression or death, whichever occurs first (up to approximately 5 months)
Part 2- Number of Participants With Adverse Events (AEs)	An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.	From first dose until 100 days after last dose (Up to approximately 5 months)
Part 2- Number of Participants With Serious Adverse Events (SAEs)	A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability or permanent damage, is a congenital anomaly/birth defect, is an important medical event.	From first dose until 100 days after last dose (Up to approximately 5 months)
Part 2- Number of Participants With AEs Leading to Discontinuation	An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.	From first dose until 100 days after last dose (Up to approximately 5 months)
Part 2- Number of Participants Who Died	Death due to any cause was assessed.	From first dose until 100 days after last dose (Up to approximately 5 months)
Part 1a and 1b - Changes From Baseline in Pharmacodynamic Biomarker	Blood samples were collected for assessing pharmacodynamic parameters.	Baseline and Cycle 1 Day 1 (Each cycle consist of 28 days)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2023
• Primary Completion (Actual): May 13, 2024
• Study Completion (Actual): May 13, 2024

Study Registration Dates

• First Submitted: August 29, 2023
• First Submitted That Met QC Criteria: August 29, 2023
• First Posted (Actual): September 6, 2023

Study Record Updates

• Last Update Posted (Actual): July 22, 2025
• Last Update Submitted That Met QC Criteria: July 20, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Colorectal cancer; Non-small cell lung cancer; Biliary tract cancer; BMS-986466; KRAS G12C-mutant; Pancreatic duct adenocarcinoma
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Cetuximab; Adagrasib
• Other Study ID Numbers: CA126-0015; 2023-505070-15 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myers Squibb's data sharing policy and process can be found at: https://www.bms.com/researchers-and-partners/clinical-trials-and-research/disclosure-commitment.html
• IPD Sharing Time Frame: See Plan Description
• IPD Sharing Access Criteria: See Plan Description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No